Teclistamab for Relapsed or Refractory Multiple Myeloma

Recent clinical trials have established the efficacy of chimeric antigen receptor (CAR) T-cell and T-cell–engaging bispecific antibodies that cotarget myeloma cell-surface antigens. Now, investigators report the multicenter, industry-funded, phase 1–2 MajesTEC-1 study of teclistamab, a bispecific antibody that binds CD3 on T cells and the B-cell maturation antigen on myeloma cells.

Patients with refractory or relapsed disease after at least three lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody) received weekly subcutaneous injections of teclistamab. An initial stepped-up dosing phase and the first full dose were given in hospital to mitigate cytokine release syndrome (CRS).

A total of 165 patients with a median of 5 prior lines of therapy were treated; most had triple-class refractory disease. During a median follow-up of 14.1 months, 63% had a partial response or better — the primary outcome — and 39% had a complete response or better. The median duration of response was 18.4 months. Nearly 27% of all patients and 46% of those with a complete response had no detectable minimal residual disease.

Most patients experienced a grade 3 or 4 adverse event, including infections (49%), neutropenia (64%), anemia, and thrombocytopenia. Of 119 CRS events, all but one was grade 1 or 2. Twenty-four patients experienced neurotoxic events, including five patients with immune effector cell–associated neurotoxicity syndrome (ICANS); all these events were low grade, aside from seizure in one patient.